1. Field of the Invention
This invention relates to specially formulated capsules of pepstatin for use in man by oral administration to inhibit pepsin in the stomach.
2. Description of the Prior Art
Pepstatin is a generic name of a group of compounds which have the following structure (T. Aoyagi and H. Umezawa, Protease and Biological Control, p. 429-454, 1975, Cold Spring Harbor Laboratory): RCO-L-Val-L-Val-AHMHA-L-Ala-AHMHA, where AHMHA is (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid. Pepstatin inhibits pepsin and cathepsin D very strongly. It also exhibits a relative strong inhibiton against renin. Among pepstatin group compounds, biological activities have been studied most in detail on that which contains isopentanoyl group as RCO--. This compound has been shown by clinical studies to be useful in treatment of gastric and duodenal ulcers in humans.
Adminstration of ordinary capsules containing pepstatin four to seven times per day has been shown to exhibit a therapeutic effect against gastric and duodenal ulcers. It has never shown any toxic signs. In this procedure an amount of pepstatin sufficient to suppress pepsin stayed for one hour in the stomach (T. Aoyagi, S. Kunimoto, H. Morishima, T. Takeuchi and H. Umezawa, Journal of Antibiotics 24, 687-694, 1971). For additional information on pepstatin see U.S. Pat. Nos. 3,740,319; 3,869,347; 3,063,579; 3,975,366 and J. Antibiotics 23, 259-262 and 263-265 (1970).
Although administration of pepstatin placed in ordinary capsules showed the desired effect, it was hoped to develop a new preparation which would permit pepstatin to stay longer in the stomach.